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Article: Pembrolizumab (Keytruda)
Title | Pembrolizumab (Keytruda) |
---|---|
Authors | |
Keywords | Lymphoma Melanoma Nonsmall cell lung cancer PD1 PDL1 PDL2 Pembrolizumab Solid tumors |
Issue Date | 2016 |
Citation | Human Vaccines & Immunotherapeutics, 2016, v. 12 n. 11, p. 2777-2789 How to Cite? |
Abstract | Abstract The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50% could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment. |
Description | Link to Free access |
Persistent Identifier | http://hdl.handle.net/10722/232071 |
ISSN | 2023 Impact Factor: 4.1 2023 SCImago Journal Rankings: 0.927 |
ISI Accession Number ID |
DC Field | Value | Language |
---|---|---|
dc.contributor.author | Kwok, G | - |
dc.contributor.author | Yau, TCC | - |
dc.contributor.author | Chiu, WYJ | - |
dc.contributor.author | Tse, EWC | - |
dc.contributor.author | Kwong, YL | - |
dc.date.accessioned | 2016-09-20T05:27:30Z | - |
dc.date.available | 2016-09-20T05:27:30Z | - |
dc.date.issued | 2016 | - |
dc.identifier.citation | Human Vaccines & Immunotherapeutics, 2016, v. 12 n. 11, p. 2777-2789 | - |
dc.identifier.issn | 2164-5515 | - |
dc.identifier.uri | http://hdl.handle.net/10722/232071 | - |
dc.description | Link to Free access | - |
dc.description.abstract | Abstract The programmed cell death protein 1 (PD1) is one of the checkpoints that regulates the immune response. Ligation of PD1 with its ligands PDL1 and PDL2 results in transduction of negative signals to T-cells. PD1 expression is an important mechanism contributing to the exhausted effector T-cell phenotype. The expression of PD1 on effector T-cells and PDL1 on neoplastic cells enables tumor cells to evade anti-tumor immunity. Blockade of PD1 is an important immunotherapeutic strategy for cancers. Pembrolizumab (Keytruda) is a humanized monoclonal anti-PD1 antibody that has been extensively investigated in numerous malignancies. In melanoma refractory to targeted therapy, pembrolizumab induced overall response rates (ORRs) of 21-34%. It was superior to another immune checkpoint inhibitor ipilimumab (Yervoy) in stage III/IV unresectable melanoma. In refractory non-small cell lung cancer (NSCLC), pembrolizumab induced ORRs of 19-25%. Based on these results, pembrolizumab was approved by the USA FDA for the treatment of advanced melanoma and NSCLC. Tumor cell PDL1 expression may be a valid response predictor. Molecular analysis also showed that tumors with high gene mutation burdens, which might result in the formation of more tumor-related neo-antigens, had better responses to pembrolizumab. In malignancies including lymphomas and other solid tumors, preliminary data showed that ORRs of around 20-50% could be achieved. Adverse events occurred in up to 60% of patients, but grade 3/4 toxicities were observed in <10% of cases. Immune-related adverse events including thyroid dysfunction, hepatitis and pneumonitis are more serious and may lead to cessation of treatment. | - |
dc.language | eng | - |
dc.relation.ispartof | Human Vaccines & Immunotherapeutics | - |
dc.subject | Lymphoma | - |
dc.subject | Melanoma | - |
dc.subject | Nonsmall cell lung cancer | - |
dc.subject | PD1 | - |
dc.subject | PDL1 | - |
dc.subject | PDL2 | - |
dc.subject | Pembrolizumab | - |
dc.subject | Solid tumors | - |
dc.title | Pembrolizumab (Keytruda) | - |
dc.type | Article | - |
dc.identifier.email | Yau, TCC: tyaucc@hku.hk | - |
dc.identifier.email | Chiu, WYJ: jwychiu@hku.hk | - |
dc.identifier.email | Tse, EWC: ewctse@hku.hk | - |
dc.identifier.email | Kwong, YL: ylkwong@hkucc.hku.hk | - |
dc.identifier.authority | Yau, TCC=rp01466 | - |
dc.identifier.authority | Chiu, WYJ=rp01917 | - |
dc.identifier.authority | Tse, EWC=rp00471 | - |
dc.identifier.authority | Kwong, YL=rp00358 | - |
dc.description.nature | link_to_subscribed_fulltext | - |
dc.identifier.doi | 10.1080/21645515.2016.1199310 | - |
dc.identifier.scopus | eid_2-s2.0-85009785163 | - |
dc.identifier.hkuros | 266596 | - |
dc.identifier.volume | 12 | - |
dc.identifier.issue | 11 | - |
dc.identifier.spage | 2777 | - |
dc.identifier.epage | 2789 | - |
dc.identifier.eissn | 2164-554X | - |
dc.identifier.isi | WOS:000388736900021 | - |
dc.identifier.issnl | 2164-5515 | - |